Infect Immun. 2013 Nov 11. [Epub ahead of print]
NLRP1 is an inflammasome sensor for Toxoplasma gondii
Department of Microbiology and Immunology, Stanford School of Medicine, Stanford, California, USA.
The obligate intracellular parasite Toxoplasma gondii is able to infect nearly all nucleated cell types of warm-blooded animals. This is achieved through the injection of hundreds of parasite effectors into the host cell cytosol allowing the parasite to establish a vacuolar niche for growth, replication and persistence. Here we show that Toxoplasma infection actives an inflammasome response in mice and rats, an innate immune sensing system designed to survey the host cytosol for foreign components leading to inflammation and cell death. Oral infection with Toxoplasma triggers an inflammasome response that is protective to the host, limiting parasite load and dissemination. Toxoplasma infection is sufficient to generate an inflammasome response in germ-free animals. IL-1β secretion by macrophage requires the effector caspases-1 and -11, the adapter ASC and NLRP1, the sensor previously described to initiate the inflammasome response to Bacillus anthracis lethal factor. The allele of NLRP1b derived from 129 mice is sufficient to enhance the B6 BMDM inflammasome response to Toxoplasma independent of the lethal factor proteolysis site. Moreover, N-terminal processing of NLRP1b, the only mechanism of activation known to date, is not observed in response to Toxoplasma infection. Cumulatively, these data indicate that NLRP1 is an innate immune sensor for Toxoplasma infection, activated via a novel mechanism that corresponds with a host-protective innate immune response to the parasite.
- [PubMed - as supplied by publisher]